The NIHR BioResource Rare Diseases BRIDGE consortium sequencing projects

The NIHR BioResource Rare Diseases BRIDGE consortium is a collaboration between 13 Rare Disease projects that aim to discover the genetic sequence variants underlying unresolved inherited disorders and to improve identification of already identified high penetrance variants. BRIDGE projects cover a variety of rare disease research areas including Cardiovascular, Infection and Immunity and Neuroscience. The consortium aims to sequence 8,000 samples across the different projects by 2017.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

23 Datasets 16 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001002070	Whole genome sequencing CRAM files for four samples from the BRIDGE Consortium (SPEED project) with pathogenic variants in a gene associated with a movement disorder.	Illumina HiSeq 2000	4
EGAD00001002656	Whole exome sequencing BAM files and whole genome sequencing CRAM files for 722 individuals from the NIHR-BioResource Rare Diseases Consortium (SPEED project) with inherited retinal disease.	Illumina HiSeq 2000	707
EGAD00001002730	SPEED - childhood dystonia KMT2B dataset	Illumina HiSeq 2000	5
EGAD00001003423	Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within genes encoding components of the transforming growth factor-ß pathway underlie the majority of heritable forms of PAH. Identifying the missing genetic contribution is challenging, even with genes of large effect size, since it likely involves mutations in genes confined to small numbers of PAH cases. In this study, we performed whole genome sequencing, comparing 1038 PAH index cases to 6385 subjects with other rare diseases. Rare variant analysis identified mutations in novel causal genes, namely ATP13A3, AQP1 and SOX17, and provided independent validation of a critical role for GDF2 in PAH. We detected mutations predicted to be disruptive of function in most, but not all, previously reported PAH genes. Taken together these findings provide new insights into the molecular basis of PAH, and support a central role for endothelial dysregulation in disease pathogenesis.	Illumina HiSeq 2000	149
EGAD00001003809	This dataset includes 186 whole genome sequencing samples which combine to create 93 pairs. Each pair is comprised of two sequencing experiments carried out on the same donor to the NIHR BioResource Rare Disease cohort. These samples have been used to validate the Telomerecat method (a method for estimating telomere length from whole genome sequencing).	Illumina HiSeq 2000	52
EGAD00001004088	Multiple primary tumors (MPT) affect a substantial proportion of cancer survivors and may result from various causes including inherited predisposition. Currently, germline genetic testing of MPT cases for cancer predisposition gene (CPG) variants is mostly targeted by tumor type. We ascertained pre-assessed MPT cases from genetics centers (defined as ≥2 primaries by age 60 years or ≥3 by 70) and performed whole genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment/molecular investigations, pathogenic variants in moderate and high-risk CPGs were detected in 67/440 (15.2%) of probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies including structural variants at low frequency (6/440 (1.4%) of probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant) the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice site CPG variants and at least one discordant tumor type was significantly higher than a control population (χ2=43.642 P=<0.0001). 2/67 (3%) of probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Summing together variant detection rates from a similarly ascertained previous MPT case series, the present results suggest that first-line comprehensive CPG analysis in a clinical genetics referral-based MPT cohort would detect a deleterious variant in about a third of cases.	Illumina HiSeq 2000	81
EGAD00001004456	This dataset contains short-read whole-genome sequencing data for individuals with neurodevelopmental disorders and their relatives from the NIHR-BioResource Rare Disease Consortium.	Illumina HiSeq 2000	4
EGAD00001004513	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project – Participants from the Cerebral Small Vessel Disease (CSVD) Rare Disease domain	Illumina HiSeq 2000	-
EGAD00001004514	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project – Participants from the Hypertrophic Cardiomyopathy (HCM) Rare Disease domain	Illumina HiSeq 2000	-
EGAD00001004515	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project.Participants from the Intrahepatic Cholestasis of Pregnancy (ICP) Rare Disease domain	Illumina HiSeq 2000	2
EGAD00001004516	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project – Participants from the Neuropathic Pain Disorders (NPD) Rare Disease domain	Illumina HiSeq 2000	-
EGAD00001004517	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project – Participants from the Primary Membranoproliferative Glomerulonephritis (PMG) Rare Disease domain	Illumina HiSeq 2000	-
EGAD00001004518	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project – Participants from the Steroid Resistant Nephrotic Syndrome (SRNS) Rare Disease domain	Illumina HiSeq 2000	-
EGAD00001004519	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project – Participants from the Bleeding, Thrombotic and Platelet Disorders (BPD) Rare Disease domain	Illumina HiSeq 2000	1
EGAD00001004520	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project – Participants from the Inherited Retinal Disorders (IRD) Rare Disease domain	Illumina HiSeq 2000	-
EGAD00001004521	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project – Participants from the Multiple Primary Malignant Tumours (MPMT) Rare Disease domain	Illumina HiSeq 2000	-
EGAD00001004522	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project – Participants from the Neurological and Developmental Disorders (NDD) Rare Disease domain	Illumina HiSeq 2000	-
EGAD00001004523	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project.Participants from the Primary Immune Disorders (PID) Rare Disease domain	Illumina HiSeq 2000	-
EGAD00001004524	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project – Participants from the Stem cell and Myeloid Disorders (SMD) Rare Disease domain	Illumina HiSeq 2000	-
EGAD00001004525	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project – Participants from the Pulmonary Arterial Hypertension (PAH) Rare Disease domain	Illumina HiSeq 2000	-
EGAD00001005122	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project – Participants from the Leber Hereditary Optic Neuropathy (LHON) Rare Disease domain	Illumina HiSeq 2000	-
EGAD00001005123	Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project – Participants from the Ehler-Danlos (ED) and ED-like Syndromes (EDS) Rare Disease domain.	Illumina HiSeq 2000	-
EGAD00001007885	Short read whole genome sequencing (WGS) VCF files for the NIHR BioResource Rare Diseases WGS project – Participants from the Hypertrophic Cardiomyopathy (HCM) Rare Disease domain		-

Publications	Citations
Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease. Carss KJ, Arno G, Erwood M, Stephens J, Sanchis-Juan A, Hull S, Megy K, Grozeva D, Dewhurst E, Malka S, Plagnol V, Penkett C, Stirrups K, Rizzo R, Wright G, Josifova D, Bitner-Glindzicz M, Scott RH, Clement E, Allen L, Armstrong R, Brady AF, Carmichael J, Chitre M, Henderson RHH, Hurst J, MacLaren RE, Murphy E, Paterson J, Rosser E, Thompson DA, Wakeling E, Ouwehand WH, Michaelides M, Moore AT, NIHR-BioResource Rare Diseases Consortium, Webster AR, Raymond FL. Am J Hum Genet 100: 2017 75-90	335
Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data. Farmery JHR, Smith ML, NIHR BioResource - Rare Diseases, Lynch AG. Sci Rep 8: 2018 1300	51
Identification of rare sequence variation underlying heritable pulmonary arterial hypertension. Gräf S, Haimel M, Bleda M, Hadinnapola C, Southgate L, Li W, Hodgson J, Liu B, Salmon RM, Southwood M, Machado RD, Martin JM, Treacy CM, Yates K, Daugherty LC, Shamardina O, Whitehorn D, Holden S, Aldred M, Bogaard HJ, Church C, Coghlan G, Condliffe R, Corris PA, Danesino C, Eyries M, Gall H, Ghio S, Ghofrani HA, Gibbs JSR, Girerd B, Houweling AC, Howard L, Humbert M, Kiely DG, Kovacs G, MacKenzie Ross RV, Moledina S, Montani D, Newnham M, Olschewski A, Olschewski H, Peacock AJ, Pepke-Zaba J, Prokopenko I, Rhodes CJ, Scelsi L, Seeger W, Soubrier F, Stein DF, Suntharalingam J, Swietlik EM, Toshner MR, van Heel DA, Vonk Noordegraaf A, Waisfisz Q, Wharton J, Wort SJ, Ouwehand WH, Soranzo N, Lawrie A, Upton PD, Wilkins MR, Trembath RC, Morrell NW. Nat Commun 9: 2018 1416	261
Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes. Whitworth J, Smith PS, Martin JE, West H, Luchetti A, Rodger F, Clark G, Carss K, Stephens J, Stirrups K, Penkett C, Mapeta R, Ashford S, Megy K, Shakeel H, Ahmed M, Adlard J, Barwell J, Brewer C, Casey RT, Armstrong R, Cole T, Evans DG, Fostira F, Greenhalgh L, Hanson H, Henderson A, Hoffman J, Izatt L, Kumar A, Kwong A, Lalloo F, Ong KR, Paterson J, Park SM, Chen-Shtoyerman R, Searle C, Side L, Skytte AB, Snape K, Woodward ER, NIHR BioResource Rare Diseases Consortium, Tischkowitz MD, Maher ER. Am J Hum Genet 103: 2018 3-18	46
Complex structural variants in Mendelian disorders: identification and breakpoint resolution using short- and long-read genome sequencing. Sanchis-Juan A, Stephens J, French CE, Gleadall N, Mégy K, Penkett C, Shamardina O, Stirrups K, Delon I, Dewhurst E, Dolling H, Erwood M, Grozeva D, Stefanucci L, Arno G, Webster AR, Cole T, Austin T, Branco RG, Ouwehand WH, Raymond FL, Carss KJ. Genome Med 10: 2018 95	107
Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses. Spencer S, Köstel Bal S, Egner W, Lango Allen H, Raza SI, Ma CA, Gürel M, Zhang Y, Sun G, Sabroe RA, Greene D, Rae W, Shahin T, Kania K, Ardy RC, Thian M, Staples E, Pecchia-Bekkum A, Worrall WPM, Stephens J, Brown M, Tuna S, York M, Shackley F, Kerrin D, Sargur R, Condliffe A, Tipu HN, Kuehn HS, Rosenzweig SD, Turro E, Tavaré S, Thrasher AJ, Jodrell DI, Smith KGC, Boztug K, Milner JD, Thaventhiran JED. J Exp Med 216: 2019 1986-1998	131
Rare Genetic Variation in 135 Families With Family History Suggestive of X-Linked Intellectual Disability. Sanchis-Juan A, Bitsara C, Low KY, Carss KJ, French CE, Spasic-Boskovic O, Jarvis J, Field M, Raymond FL, Grozeva D. Front Genet 10: 2019 578	4
Large-Scale Whole-Genome Sequencing Reveals the Genetic Architecture of Primary Membranoproliferative GN and C3 Glomerulopathy. Levine AP, Chan MMY, Sadeghi-Alavijeh O, Wong EKS, Cook HT, Ashford S, Carss K, Christian MT, Hall M, Harris CL, McAlinden P, Marchbank KJ, Marks SD, Maxwell H, Megy K, Penkett CJ, Mozere M, Stirrups KE, Tuna S, Wessels J, Whitehorn D, MPGN/DDD/C3 Glomerulopathy Rare Disease Group, NIHR BioResource, Johnson SA, Gale DP. J Am Soc Nephrol 31: 2020 365-373	30
Monoallelic loss-of-function THPO variants cause heritable thrombocytopenia. Cornish N, Aungraheeta MR, FitzGibbon L, Burley K, Alibhai D, Collins J, Greene D, Downes K, NIHR BioResource, Westbury SK, Turro E, Mumford AD. Blood Adv 4: 2020 920-924	10
Structural analysis of pathogenic missense mutations in GABRA2 and identification of a novel de novo variant in the desensitization gate. Sanchis-Juan A, Sanchis-Juan A, Hasenahuer MA, Baker JA, McTague A, Barwick K, Kurian MA, Duarte ST, NIHR BioResource, Carss KJ, Thornton J, Raymond FL. Mol Genet Genomic Med 8: 2020 e1106	7
Whole-genome sequencing of a sporadic primary immunodeficiency cohort. Thaventhiran JED, Lango Allen H, Burren OS, Rae W, Greene D, Staples E, Zhang Z, Farmery JHR, Simeoni I, Rivers E, Maimaris J, Penkett CJ, Stephens J, Deevi SVV, Sanchis-Juan A, Gleadall NS, Thomas MJ, Sargur RB, Gordins P, Baxendale HE, Brown M, Tuijnenburg P, Worth A, Hanson S, Linger RJ, Buckland MS, Rayner-Matthews PJ, Gilmour KC, Samarghitean C, Seneviratne SL, Sansom DM, Lynch AG, Megy K, Ellinghaus E, Ellinghaus D, Jorgensen SF, Karlsen TH, Stirrups KE, Cutler AJ, Kumararatne DS, Chandra A, Edgar JDM, Herwadkar A, Cooper N, Grigoriadou S, Huissoon AP, Goddard S, Jolles S, Schuetz C, Boschann F, Primary Immunodeficiency Consortium for the NIHR Bioresource, Lyons PA, Hurles ME, Savic S, Burns SO, Kuijpers TW, Turro E, Ouwehand WH, Thrasher AJ, Smith KGC. Nature 583: 2020 90-95	130
Whole-genome sequencing of patients with rare diseases in a national health system. Turro E, Astle WJ, Megy K, Gräf S, Greene D, Shamardina O, Allen HL, Sanchis-Juan A, Frontini M, Thys C, Stephens J, Mapeta R, Burren OS, Downes K, Haimel M, Tuna S, Deevi SVV, Aitman TJ, Bennett DL, Calleja P, Carss K, Caulfield MJ, Chinnery PF, Dixon PH, Gale DP, James R, Koziell A, Laffan MA, Levine AP, Maher ER, Markus HS, Morales J, Morrell NW, Mumford AD, Ormondroyd E, Rankin S, Rendon A, Richardson S, Roberts I, Roy NBA, Saleem MA, Smith KGC, Stark H, Tan RYY, Themistocleous AC, Thrasher AJ, Watkins H, Webster AR, Wilkins MR, Williamson C, Whitworth J, Humphray S, Bentley DR, NIHR BioResource for the 100,000 Genomes Project, Kingston N, Walker N, Bradley JR, Ashford S, Penkett CJ, Freson K, Stirrups KE, Raymond FL, Ouwehand WH. Nature 583: 2020 96-102	332
Development and validation of a universal blood donor genotyping platform: a multinational prospective study. Gleadall NS, Veldhuisen B, Gollub J, Butterworth AS, Ord J, Penkett CJ, Timmer TC, Sauer CM, van der Bolt N, Brown C, Brugger K, Dilthey AT, Duarte D, Grimsley S, van den Hurk K, Jongerius JM, Luken J, Megy K, Miflin G, Nelson CS, Prinsze FJ, Sambrook J, Simeoni I, Sweeting M, Thornton N, Trompeter S, Tuna S, Varma R, Walker MR, NIHR BioResource, Danesh J, Roberts DJ, Ouwehand WH, Stirrups KE, Rendon A, Westhoff CM, Di Angelantonio E, van der Schoot CE, Astle WJ, Watkins NA, Lane WJ. Blood Adv 4: 2020 3495-3506	27
GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements. Dixon PH, Levine AP, Cebola I, Chan MMY, Amin AS, Aich A, Mozere M, Maude H, Mitchell AL, Zhang J, NIHR BioResource, Genomics England Research Consortium Collaborators, Chambers J, Syngelaki A, Donnelly J, Cooley S, Geary M, Nicolaides K, Thorsell M, Hague WM, Estiu MC, Marschall HU, Gale DP, Williamson C. Nat Commun 13: 2022 4840	18
Genome sequencing and comprehensive rare-variant analysis of 465 families with neurodevelopmental disorders. Sanchis-Juan A, Megy K, Stephens J, Armirola Ricaurte C, Dewhurst E, Low K, French CE, Grozeva D, Stirrups K, Erwood M, McTague A, Penkett CJ, Shamardina O, Tuna S, Daugherty LC, Gleadall N, Duarte ST, Hedrera-Fernández A, Vogt J, Ambegaonkar G, Chitre M, Josifova D, Kurian MA, Parker A, Rankin J, Reid E, Wakeling E, Wassmer E, Woods CG, NIHR BioResource, Raymond FL, Carss KJ. Am J Hum Genet 110: 2023 1343-1355	9
The role of genetic sequencing in the diagnostic workup for chronic immune thrombocytopenia. Joshi N, Lango-Allen H, Downes K, Simeoni I, Vladescu C, Paul D, Hart A, Ademokun C, Cooper N. Blood Adv 9: 2025 1497-1507	0